Beginning in about 1990, many potentially harmful interactions between drugs and even between drugs and foods (such as grapefruit juice) were noted with Seldane and other drugs. The discovery led to greater attention by the FDA and drug manufacturers to such interactions before drugs are marketed. This represents a significant enhancement of safety assessment.

When Other Risk Management Options Fail

When you hear news about a drug coming off the market, it may appear to be a sudden, drastic step. But several other options to manage risks usually have been attempted before that point. The main risk management tools employed by the FDA are education through letters to health-care professionals (known within the FDA as "Dear Doctor" letters) and labeling changes, such as new warnings, sometimes boxed in black for emphasis. Also used are required Medication Guides, labeling specifically for patients that emphasizes significant risks and advises patients how to detect or avoid them.

In some cases, a drug is labeled as "second line," meaning it is to be used only in patients for whom other treatments fail. In other cases, a drug that is known to be dangerous is still made available under certain circumstances through what's known as restricted distribution.

Sometimes these risk management techniques are effective, and other times they are not. Unfortunately, there has been little systematic study of the effect of drug labeling changes on physician behavior.